Dactolisib (BEZ235, NVP-BEZ235)

目录号:S1009

Dactolisib (BEZ235, NVP-BEZ235) Chemical Structure

Molecular Weight(MW): 469.55

Dactolisib (BEZ235, NVP-BEZ235) 是一种双重ATP竞争性 PI3KmTOR 抑制剂,在无细胞试验中,抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。 在 3T3TopBP1-ER 细胞中抑制 ATR,IC50 为 21 nM,而对 Akt 和 PDK1 的抑制作用很弱。Phase 2。

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RMB 1414.41 现货
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客户购买Selleck的此次产品后发表的文献82篇:

客户使用该产品的11个实验数据:

  • Level of phospho-proteins in RTK and PI3K–Akt–mTOR pathways in treated tumours, detected with western blot.

    Nature, 2017, 728-732. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Relative kinase activities of p110α mutants and the inhibitory effect of PI3K inhibitors against hotspot mutants of p110α. A, recombinant FLAG-tagged PI3K p110α/p85α protein complex produced in 293T cells was immunoprecipitated , and the immunoprecipitates were used for the quantitative PI3K-HTRF assay (32).

    B, effect of three PI3K inhibitors (ZSTK474, LY294002, and NVP-BEZ235) on the enzymatic activity of two hotspot mutants (E545K and H1047R) p110α compared with the wild-type. No striking difference was observed in the IC50 concentrations of these inhibitors between wild-type and mutant p110α.
     

     

    Cancer Res 2010 70, 4982-4994. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • A, ANOVA of IC50 values of the dual PI3K/mTOR inhibitor NVP-BEZ235 in 23 melanoma cell lines showing no significant difference in sensitivity to this compound in B-Raf mutant and Braf wild-type cells. B, decreases in pAkt and pP70S6K in a dose and time-dependent fashion in 2 melanoma cell lines treated with NVP-BEZ235. pP70S6K levels are undetectable at all concentrations and time points studied, whereas levels of pAkt start rising again after 4 hours of drug exposure in a dose-dependent fashion. C, clonogenic assays in 2 melanoma cell lines (YUVON and YUSIK) treated with NVP-BEZ235 at different concentrations. NVPBEZ235 was effective in inhibiting colony formation at low nanomolar concentrations.

    Clin Cancer Res 2010 16, 6029-6039. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    Three-dimensional responses of MCF7/IGF-1R cells to TAM (1 μM), E2 and IGF-1. Compared to parental MCF7 cells (a), MCF7/IGF-1R cells (b) in three-dimensional (3D) culture formed bigger acini in response to IGF-1 stimulation and displayed significant TAM resistance when treated with TAM (1 μM) + E2 + IGF-1, which was removable by kinase inhibitors BMS-536924, U0126 and BEZ235 (c). Cells (10,000/well) were seeded in 96-well plates. Acini were formed on 100% Matrigel and cultured for 14 days in starving medium containing 2% Matrigel and 5% charcoal/dextran-stripped fetal bovine serum with the treatments as indicated. Concentrations used: TAM (1 μM), E2 (1 nM) and IGF-1 (100 ng/mL). Confocal image original magnification, × 20. Red, rhodamine phalloidin (actin). Blue, Hoechst blue stain. Results are representative of two individual experiments.

    Breast Cancer Res 2011 13, R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • TAM (10 nM) agonistic behavior in MCF7/IGF-1R cells is not inhibited by phosphatidylinositol 3-kinase/Akt inhibitor BEZ235. (a) Inhibitory effects of kinase inhibitors BMS-536924, U0126 and BEZ235 on agonistic effect of TAM (10 nM) in the presence of IGF-1 (100 ng/mL). **P < 0.01. (b) Inhibitory effects of phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor BEZ235 at various dose ranges on IGF-1R signaling. (c) Agonistic behavior of TAM (10 nM) in response to BEZ235 kinase inhibitor. (-), no BEZ235. Results are representative of three independent experiments. Data are expressed as means ± SD.

    Breast Cancer Res 2011 13:R52. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    ZSTK474 and GDC-0941 selectively inhibit class I PI3K over mTOR. (A) Inhibition profiles of the selected five PI3K inhibitors for mTOR. Data shown are mean±SD (n = 3), representative of 2 or 3 independent experiments. (B) IC50 values of the PI3K inhibitors for mTOR. (C) Selectivity of each PI3K inhibitor for PI3Ka over mTOR. The selectivity index is expressed as the ratio of the IC50 value for mTOR over that for PI3Ka. The IC50 values of ZSTK474, NVP-BEZ235 and LY294002 for PI3Ka are 0.016, 0.007 and 0.6 μM, respectively, as reported previously by us.

     

     

    Eur J Cancer 2010 46, 1111-1121. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  • (B) The effects of AZD2014, BEZ235, lapatinib, LEE011, pazopanib on PI3K/AKT signaling in sarcoma PDC line were determined by immunoblotting analysis. Cells were treated with 1 μM of the indicated drugs for 72 h.

    Transl Oncol, 2016, 9(3):197-202. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    The effects of LY294002, rapamycin and NVP-BEZ235 on activation of PI3K-Akt-mTOR pathway in hepatocytes. (a) The mRNA expression (PI3K, Akt, mTOR, raptor) by Real-Time PCR, (b) protein expression (PI3K, Akt, mTOR, S6K) by ELISA kits; (c) protein expression of S6K and P-S6K by western blotting. The different letters indicated significant differences (P <0.05). LY = LY294002; rapa = rapamycin; NVP = NVP-BEZ235.

    Animal, 2016, 10(8):1319-27. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

    After starved in serum-free medium for 24h,breast cancer cells incubated with the indicated concentrations of BEZ235 for 3h,followed by 20-minute  stimulation of 100ng/ml EGF.

     

     

    Dr. Zhang of Tianjin Medical University. Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

  •  

    FIG. 4. Phospholipase A2 group 4A (PLA2G4A) expression was increased after BEZ235 treatment in basal-like xenografts. The bar graph shows the quantification of the immunoblots (mean±SD). PLA2G4A, Ethanolamine kinase 1 and 2 (ETNK1/2), Choline kinase alpha/beta (ChoKA/B), and β-actin protein expression were examined by immunoblotting of tissue samples after MRS experiments [control group (n= 5) and BEZ235-treated group (n=7)]. This demonstrated a higher expression of PLA2G4A protein ( P=0.005), but no changes in ETNK1 and ChoKA/B in samples from basal-like xenografts treated with BEZ235.

    Dactolisib (BEZ235, NVP-BEZ235) purchased from Selleck.

产品安全说明书

PI3K抑制剂选择性比较

生物活性

产品描述 Dactolisib (BEZ235, NVP-BEZ235) 是一种双重ATP竞争性 PI3KmTOR 抑制剂,在无细胞试验中,抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。 在 3T3TopBP1-ER 细胞中抑制 ATR,IC50 为 21 nM,而对 Akt 和 PDK1 的抑制作用很弱。Phase 2。
靶点
p110α [1]
(Cell-free assay)
p110γ [1]
(Cell-free assay)
mTOR (p70S6K) [1]
(Cell-free assay)
p110δ [1]
(Cell-free assay)
ATR [8]
(3T3TopBP1-ER cells)
4 nM 5 nM 6 nM 7 nM 21 nM
体外研究

BEZ235显著降低mTOR活化的激酶p70S6K的磷酸化水平。BEZ235导致S235/S236P-RPS6水平减少,IC50为6.5 nM。BEZ235抗mTOR的活性使用生化mTOR K-LISA试验测定,IC50为20.7 nM。BEZ235对其β旁系同源物的活性稍弱,IC50为75 nM。在人肿瘤细胞中,PI3K/Akt/mTOR通路经常被组成性活化。BEZ235阻断PI3K和mTOR激酶活性,通过结合于这些酶的ATP结合槽发挥作用。用逐渐增加浓度BEZ235处理PTEN-null细胞系PC3M和U87MG时,导致细胞增殖剂量依赖性减少,平均GI50为10-12 nM。[1] BEZ235是一种mTORC1/2催化抑制剂。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Trypanosoma brucei brucei NWi5U2dQSW62aX3pZ5Jw[mmjbDDBd5NigQ>? NILEVIMyQCCq NEC4SlVFVVOR NHTPfHhCdnSrdIL5dIFvd3OxbXHsJIFkfGm4aYT5JJdqfGhiRVO1NEBw\iByLkCwNlUh|ryP MYOyOFgxPTl2Nh?=
MCF7 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfzNE4xOS1zMECg{txO M4TVSFQ5KGh? NULaXFN7TE2VTx?= Mlj0TWM2OD1yLkezJO69VQ>? NFOzXG4zOzh5MUmwOC=>
HCT116 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3TcJIxNjBzLUGwNEDPxE1? MUm0PEBp NIPLZ2tFVVOR NFm5SGtKSzVyPUGuNVYh|ryP M1[yb|I{QDdzOUC0
U87MG NInBZmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnvNE4xOS1zMECg{txO MXy0PEBp MmjQSG1UVw>? NH;yd|JKSzVyPUGuN|Ih|ryP MUmyN|g4OTlyNB?=
HBC4 NGPvWopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV6wMlAyNTFyMDFOwG0> NXzXWVF[PDhiaB?= NGrEb2FNd2diR1m1NF0uQC54MTDN M1qyRlIzOzN4MkS2
BSY1 NU\6UmxxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{K3V|AvODFvMUCwJO69VQ>? MnjJOFghcA>? NY\ifVJRVG:pIFfJOVA:NThwNEigUS=> M33jZ|IzOzN4MkS2
HBC5 MkG3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkC4NE4xOS1zMECg{txO MXK0PEBp M4jINGxw\yCJSUWwQU04Njh5IF2= MoPDNlI{OzZ{NE[=
MCF7 MlTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHTSXMxNjBzLUGwNEDPxE1? MUO0PEBp NX\x[nE4VG:pIFfJOVA:NThwMU[gUS=> NUnDd2E4OjJ|M{[yOFY>
MDA-MB-231 NWe0Noo2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\INE4xOS1zMECg{txO MUG0PEBp Mni2UI9oKEeLNUC9MVgvODliTR?= NXm2XGFOOjJ|M{[yOFY>
U251 NWmwcnlbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPoNE4xOS1zMECg{txO Ml\kOFghcA>? M4jFWGxw\yCJSUWwQU04NjZ4IF2= M1LrZlIzOzN4MkS2
SF268 NVW3em55T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;MNE4xOS1zMECg{txO M{f3c|Q5KGh? M4r5OGxw\yCJSUWwQU04Njl{IF2= MYiyNlM{PjJ2Nh?=
SF295 NEj5[25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvUNE4xOS1zMECg{txO MXu0PEBp NIHtflFNd2diR1m1NF0uQC5|MTDN NFvDbXkzOjN|NkK0Oi=>
SF539 MlLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3ztPFAvODFvMUCwJO69VQ>? MnHOOFghcA>? NYTXTIpLVG:pIFfJOVA:NThwNUmgUS=> MXGyNlM{PjJ2Nh?=
SNB75 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIX4PZIxNjBzLUGwNEDPxE1? NW\DZoxSPDhiaB?= MUHMc4chT0l3ME2tPE42QCCP M{DWcFIzOzN4MkS2
SNB78 M13GOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLJe3UzOC5yMT2xNFAh|ryP M{DaUlQ5KGh? NIj1e3VNd2diR1m1NF0uQC54NTDN M1nwclIzOzN4MkS2
HCC2998 M1KwNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2\Q[VAvODFvMUCwJO69VQ>? NXrXTJQxPDhiaB?= MXPMc4chT0l3ME2tPE4xPSCP MlH5NlI{OzZ{NE[=
KM12 M{noUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{TUbFAvODFvMUCwJO69VQ>? NWXXS|ZOPDhiaB?= NE\JU|ZNd2diR1m1NF0uPy53NDDN NIDyVYYzOjN|NkK0Oi=>
HT-29 M3jL[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXqwMlAyNTFyMDFOwG0> NWHyS3hKPDhiaB?= M1X5Zmxw\yCJSUWwQU04Njd3IF2= NI\QVHIzOjN|NkK0Oi=>
HCT15 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3DZlB[OC5yMT2xNFAh|ryP MoDYOFghcA>? MkfVUI9oKEeLNUC9MVgvODNiTR?= NXPaenNoOjJ|M{[yOFY>
HCT116 M3jCfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX2wMlAyNTFyMDFOwG0> MUi0PEBp M4\xXmxw\yCJSUWwQU04NjZzIF2= MofqNlI{OzZ{NE[=
NCI-H23 Mnz6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF[4SpMxNjBzLUGwNEDPxE1? M3\HXlQ5KGh? M2[wVWxw\yCJSUWwQU04NjZ2IF2= NGXCW|gzOjN|NkK0Oi=>
NCI-H226 M4LwWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUewMlAyNTFyMDFOwG0> MlPLOFghcA>? NYXXNW9sVG:pIFfJOVA:NThwNESgUS=> NH\md3ozOjN|NkK0Oi=>
NCI-H522 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3ENE4xOS1zMECg{txO MUm0PEBp NXfERmtvVG:pIFfJOVA:NThwNEWgUS=> NVPT[mJKOjJ|M{[yOFY>
NCI-H438 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrWXpNWOC5yMT2xNFAh|ryP NF3KPXE1QCCq M37jcmxw\yCJSUWwQU05NjFzIF2= Mlf0NlI{OzZ{NE[=
A549 M4fWWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjHUmQxNjBzLUGwNEDPxE1? M1nESFQ5KGh? MofVUI9oKEeLNUC9MVgvODdiTR?= MVeyNlM{PjJ2Nh?=
DMS273 M3;sWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn\UNE4xOS1zMECg{txO NX\MU3l7PDhiaB?= M2O5XGxw\yCJSUWwQU04NjhyIF2= MXGyNlM{PjJ2Nh?=
DMS114 NHnzT|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTINE4xOS1zMECg{txO NVLERXc4PDhiaB?= NVzDWm14VG:pIFfJOVA:NThwM{mgUS=> NYDaWJRyOjJ|M{[yOFY>
LOXIMVI MkfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV23S4hOOC5yMT2xNFAh|ryP NVfpZog6PDhiaB?= MkH4UI9oKEeLNUC9MVgvPjZiTR?= NITuW|YzOjN|NkK0Oi=>
OVCAR3 MoLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWqzZXhWOC5yMT2xNFAh|ryP MYi0PEBp MWHMc4chT0l3ME2tPE4yPyCP Mln4NlI{OzZ{NE[=
OVCAR4 M2fMVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmewNE4xOS1zMECg{txO Mn34OFghcA>? M2XGOWxw\yCJSUWwQU05NjV6IF2= MlrXNlI{OzZ{NE[=
OVCAR5 Ml;RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjMNGxwOC5yMT2xNFAh|ryP MXK0PEBp M3HXTmxw\yCJSUWwQU04NjV5IF2= NFztdWczOjN|NkK0Oi=>
OVCAR8 NELZcmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXjDXmdCOC5yMT2xNFAh|ryP MW[0PEBp Mk\3UI9oKEeLNUC9MVcvQDRiTR?= MmnENlI{OzZ{NE[=
SKOV3 MmHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWWwMlAyNTFyMDFOwG0> M4PUTlQ5KGh? NXj6RnJ7VG:pIFfJOVA:NThwNEGgUS=> MYCyNlM{PjJ2Nh?=
RXF631L Mn65S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYGwMlAyNTFyMDFOwG0> MlfzOFghcA>? Mk\wUI9oKEeLNUC9MVgvOjFiTR?= MlHFNlI{OzZ{NE[=
ACHN MkjDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYC0N5Q1OC5yMT2xNFAh|ryP M4TVXlQ5KGh? NUP2V4hpVG:pIFfJOVA:NTdwOUWgUS=> MUKyNlM{PjJ2Nh?=
St-4 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fBRVAvODFvMUCwJO69VQ>? MoHqOFghcA>? MnL6UI9oKEeLNUC9MVcvPDdiTR?= MWiyNlM{PjJ2Nh?=
MKN1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzTSokxNjBzLUGwNEDPxE1? NY\zcW85PDhiaB?= NWTkOZNrVG:pIFfJOVA:NThwNEGgUS=> MknkNlI{OzZ{NE[=
MKN7 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDGNE4xOS1zMECg{txO MnvPOFghcA>? MorlUI9oKEeLNUC9MVcvPjhiTR?= NWGydZR[OjJ|M{[yOFY>
MKN28 MkPsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX2wMlAyNTFyMDFOwG0> M3HB[VQ5KGh? MkLyUI9oKEeLNUC9MVcvODdiTR?= NHTsWoYzOjN|NkK0Oi=>
MKN45 MkLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfIXYszOC5yMT2xNFAh|ryP MXO0PEBp MUDMc4chT0l3ME2tPE4{PCCP Mli1NlI{OzZ{NE[=
MKN74 NYj3Z|drT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYqwMlAyNTFyMDFOwG0> NGTtSHA1QCCq M1HLUGxw\yCJSUWwQU04NjR{IF2= MXiyNlM{PjJ2Nh?=
DU145 M{Dn[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\WcJlWOC5yMT2xNFAh|ryP M1LJelQ5KGh? NXniNY1LVG:pIFfJOVA:NThwMU[gUS=> MVOyNlM{PjJ2Nh?=
PC3 NXTJRXVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELsOlcxNjBzLUGwNEDPxE1? NFvUV281QCCq M3rI[Gxw\yCJSUWwQU05NjZ4IF2= NYPMcXN4OjJ|M{[yOFY>
Trypanosoma brucei brucei NULwbllUTnWwY4Tpc44hSXO|YYm= NWTkSo9{OjByIH7N MnPXNVIhcA>? MYLEUXNQ M{HFOGRm[3KnYYPlJIlvKHCqb4PwbI91cWS7bDDpco9{cXSxbDDwbI9{eGijdHWgcIV3\Wx? NWjlbldzOjR6MEW5OFY>
Trypanosoma brucei brucei NGfyWlhHfW6ldHnvckBCe3OjeR?= MXqxPEBp MX;EUXNQ MlvPTY5pcWKrdHnvckBw\iC{ZXPldJRwei2vZXTpZZRm\CCnbnTvZ5l1d3OrczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiC2cnHud4ZmenKrbjD1dJRic2V? M4K3[lI1QDB3OUS2
Trypanosoma brucei brucei M2POOWZ2dmO2aX;uJGF{e2G7 M1GzWFIxOCCwTR?= NUXwe|dWOTJiaB?= NEfr[nRFVVOR M1[3OGVn\mWldDDvckB{eGirbnfvcZlt\WmwIHzleoVt NIjXeWgzPDhyNUm0Oi=>
Trypanosoma brucei brucei MkLnSpVv[3Srb36gRZN{[Xl? NFnI[lQzODBibl2= NF7QPHEyOiCq NHnEUYVFVVOR M1T6cWVn\mWldDDvckBxcG:|cHjheIllgWylaH;sbY5mKGyndnXs NWDnd2ZXOjR6MEW5OFY>
UM-UC-3 M2PmTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPje4ZSUUN3ME2zNVUheE1? NFfjfndUSU6JRWK=
SBC-1 NF\TT3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHJfFBKSzVyPUe0NkBxVQ>? MYXTRW5ITVJ?
MKN1 NEPud4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTJwODDuUS=> M4O5W3NCVkeHUh?=
NCI-H720 M{\xcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTNwNUegcm0> NHXWSo1USU6JRWK=
BFTC-909 NHSxVIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;HVINKSzVyPUOuO|Ehdk1? MnrzV2FPT0WU
BPH-1 NXG4PZFLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX:y[|dQUUN3ME20Mlc3KG6P NVr3b3hRW0GQR1XS
PC-3 NVLsU4oxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7oXY5KSzVyPUWuNFkhdk1? NHLFTFVUSU6JRWK=
AN3-CA NXvtT4xOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17NdmlEPTB;NT61OkBvVQ>? M4XYTXNCVkeHUh?=
HN NVi1cmRHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4fVTWlEPTB;NT65OkBvVQ>? MWTTRW5ITVJ?
HCC2218 NVHZPGJ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTZwNkGgcm0> M2PlTnNCVkeHUh?=
KP-4 MnWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfNNplKSzVyPUegcm0> NWDXe49pW0GQR1XS
LU-139 NIe5N41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrZN4hKSzVyPUeuO|chdk1? NIrDWZNUSU6JRWK=
ETK-1 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWnJR|UxRTdwOEigcm0> NEL4TJRUSU6JRWK=
Ramos-2G6-4C10 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXSelhKSzVyPUiuOFkhdk1? M3fEc3NCVkeHUh?=
MHH-PREB-1 NXHJRXpkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTlwMUKgcm0> NXWwWpZDW0GQR1XS
DU-4475 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYHiUmV{UUN3ME25MlQ1KG6P M17kZ3NCVkeHUh?=
NCI-H1666 NXvZXJNYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3vTWM2OD17LkexJI5O MVTTRW5ITVJ?
CAMA-1 Ml3YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnHTWM2OD17Lkigcm0> MYXTRW5ITVJ?
TYK-nu NYfWPXRrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfETWM2OD17Lkm0JI5O NGnVN4NUSU6JRWK=
MFE-280 Mlv2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWLJR|UxRTlwOUmgcm0> NU\oUIVvW0GQR1XS
A549 NFvU[GFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M174OGlEPTB;MUCuNVQhdk1? MnOyV2FPT0WU
769-P NIrVc2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTFyLkS0JI5O MVPTRW5ITVJ?
L-363 MkDTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnsS|ZKSzVyPUGwMlY6KG6P NHXudYRUSU6JRWK=
ES8 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFz1UVJKSzVyPUGwMlkhdk1? Mk\5V2FPT0WU
PA-1 MnjzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfXTWM2OD1zMT64NkBvVQ>? NEnURW1USU6JRWK=
Mewo NXO0cWpuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTFzLkm5JI5O NYXUe3R5W0GQR1XS
HSC-3 M{nROWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTF{LkKxJI5O MUfTRW5ITVJ?
H4 M{S5[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTF{Lk[3JI5O NX\0clhTW0GQR1XS
BB65-RCC M1rBVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3jyN2lEPTB;MUKuO|Ihdk1? MYrTRW5ITVJ?
NCI-H1793 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7QTWM2OD1zMj64NkBvVQ>? MkjEV2FPT0WU
KARPAS-45 M4\TV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnmOXBKSzVyPUGzMlUyKG6P MULTRW5ITVJ?
GCT MkKyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLRW5A4UUN3ME2xN{43QCCwTR?= NYfwWWU1W0GQR1XS
EoL-1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELpeWJKSzVyPUGzMlk{KG6P MX3TRW5ITVJ?
LB2241-RCC Mlr4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoLhTWM2OD1zND6wNUBvVQ>? NGfrfodUSU6JRWK=
ES5 NF3SOI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVG2NWFmUUN3ME2xOE44PCCwTR?= MY\TRW5ITVJ?
LOXIMVI M3zyRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTF2Lkm5JI5O M2fTXXNCVkeHUh?=
COR-L105 NUTGdo9kT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXWNJF6UUN3ME2xOU4xPCCwTR?= MWrTRW5ITVJ?
P12-ICHIKAWA NWj6eoVDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13xU2lEPTB;MUWuNUBvVQ>? NH7SdVBUSU6JRWK=
CHL-1 NU\zNpVOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWDJR|UxRTF3LkS1JI5O Mn\XV2FPT0WU
VMRC-RCZ NUfmZmsxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2PyOGlEPTB;MUWuOlMhdk1? NEjnUZVUSU6JRWK=
HH M3P5Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rLPWlEPTB;MUWuO{BvVQ>? NWLpUm9ZW0GQR1XS
NUGC-3 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlnQTWM2OD1zNj6zOEBvVQ>? MVfTRW5ITVJ?
EGI-1 NWi0ZodLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7DflJKSzVyPUG2MlQ{KG6P MV\TRW5ITVJ?
OS-RC-2 NETSd25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\ISGlEPTB;MU[uOFchdk1? MknVV2FPT0WU
MOLT-16 M3y2S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTMTWM2OD1zNz6xOUBvVQ>? NFvtSoxUSU6JRWK=
NCI-H209 M2G4cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVi5U3E{UUN3ME2xO{4zQSCwTR?= MYXTRW5ITVJ?
697 NVHGTHVuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUG4[FRoUUN3ME2xO{41OyCwTR?= MYHTRW5ITVJ?
D-56MG MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnDbY1{UUN3ME2xO{43QSCwTR?= MXPTRW5ITVJ?
VA-ES-BJ NYrEVFNPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\6dIlKSzVyPUG3Mlg{KG6P MVrTRW5ITVJ?
EW-16 NHvSfGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NU\x[25DUUN3ME2xPE4xPCCwTR?= NF7mSmFUSU6JRWK=
HGC-27 M3zQV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjuO45KSzVyPUG4MlA3KG6P NUXKdFFPW0GQR1XS
ES7 NFvROWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXizOVZwUUN3ME2xPE4xQSCwTR?= MW\TRW5ITVJ?
HuH-7 M1u5Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXRTWM2OD1zOD60JI5O M{f0O3NCVkeHUh?=
BCPAP M2f2dWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLoTWM2OD1zOD62OUBvVQ>? M3rySnNCVkeHUh?=
SW1710 NWX6UmlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jMZ2lEPTB;MUiuO|Ihdk1? NFTWOmhUSU6JRWK=
IST-MEL1 MlXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlPTTWM2OD1zOD63O{BvVQ>? NGTIO2tUSU6JRWK=
SF295 M1r4emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mk\oTWM2OD1zOD65N{BvVQ>? NYX1XIhIW0GQR1XS
RPMI-7951 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH;Pb21KSzVyPUG5MlI5KG6P NUTneldRW0GQR1XS
SF126 M{nRR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTF7LkSxJI5O NWTYWGxtW0GQR1XS
GAMG M{TYbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYXDTo9OUUN3ME2xPU41QCCwTR?= MVLTRW5ITVJ?
KNS-81-FD NIDPcG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIP6b5hKSzVyPUG5MlU1KG6P MXLTRW5ITVJ?
RT-112 NEfLRYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTF7Lk[2JI5O NVLxVlRVW0GQR1XS
DEL NGTSTGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTJyLkS5JI5O MWLTRW5ITVJ?
CGTH-W-1 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7ITWM2OD1{MD62N{BvVQ>? NYezdoJRW0GQR1XS
HOS MlHES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRTJzLkC2JI5O NEi4ZVNUSU6JRWK=
ES4 NIT4TopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1Pzd2lEPTB;MkGuNFghdk1? NWTBXGt7W0GQR1XS
RXF393 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojqTWM2OD1{MT60OUBvVQ>? NU\CU5lEW0GQR1XS
NCI-H2030 NUjqUoFuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlf5TWM2OD1{MT61NkBvVQ>? NFPXWWNUSU6JRWK=
YH-13 MknuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXS1O4E3UUN3ME2yNU45QCCwTR?= NIrEcoVUSU6JRWK=
HT-1080 NX\UOHI3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4nYcmlEPTB;MkGuPVMhdk1? MlnSV2FPT0WU
NCI-SNU-1 Mn\PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLrSWlKSzVyPUKxMlk2KG6P MkTlV2FPT0WU
G-402 NGDNfphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHIV4pKSzVyPUKyMlE3KG6P NW\XXY41W0GQR1XS
786-0 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;VblJKSzVyPUKyMlI6KG6P MXfTRW5ITVJ?
ME-180 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjPfJJOUUN3ME2yNk41OyCwTR?= MWTTRW5ITVJ?
NB69 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfuOVVvUUN3ME2yNk42OyCwTR?= MXfTRW5ITVJ?
J-RT3-T3-5 MlzPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFjsOFlKSzVyPUKyMlk3KG6P MWnTRW5ITVJ?
TGBC1TKB NFvN[Y5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoW5TWM2OD1{Mz6wOUBvVQ>? Ml[3V2FPT0WU
SW780 NHjtVJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkP5TWM2OD1{Mz6xN{BvVQ>? Mly4V2FPT0WU
MG-63 NEPjTlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzxTWM2OD1{Mz60OUBvVQ>? MX7TRW5ITVJ?
BV-173 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1rqVWlEPTB;MkOuPFchdk1? MoSzV2FPT0WU
CAL-51 NV7YVY9QT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPKTWM2OD1{Mz64PUBvVQ>? MV3TRW5ITVJ?
A375 Mlj0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTJ|LkmzJI5O M4j1N3NCVkeHUh?=
MEL-HO MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2m0ZmlEPTB;MkSuNFQhdk1? NWHUWmJLW0GQR1XS
EFO-27 M{Plc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4LoVGlEPTB;MkSuN|Mhdk1? MYrTRW5ITVJ?
Hs-578-T NXLLV3A5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUfCS4RpUUN3ME2yOE42QCCwTR?= NFfZZY1USU6JRWK=
NBsusSR MlmxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2jPc2lEPTB;MkSuOkBvVQ>? M336cHNCVkeHUh?=
CTB-1 M3;0Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnntTWM2OD1{ND62O{BvVQ>? MkjUV2FPT0WU
FTC-133 NYDmbnJ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXte|lKSzVyPUK1MlEhdk1? MUjTRW5ITVJ?
MOLT-4 NXHwXII{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1HYeWlEPTB;MkWuNVIhdk1? MX7TRW5ITVJ?
HO-1-N-1 M{i4Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEnpWmVKSzVyPUK1MlE2KG6P M17nenNCVkeHUh?=
ES3 NFTGeXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonYTWM2OD1{NT6yNkBvVQ>? NVPFcpJlW0GQR1XS
TI-73 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnqzTWM2OD1{NT6yPEBvVQ>? NWjMdmZNW0GQR1XS
MPP-89 MofuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmKwTWM2OD1{NT6zNkBvVQ>? NHvSTZRUSU6JRWK=
KYSE-150 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfIcHFPUUN3ME2yOU45QSCwTR?= M2j0fHNCVkeHUh?=
LXF-289 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTJ4LkC0JI5O MWfTRW5ITVJ?
SK-LU-1 NEnXdmdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXXTWM2OD1{Nj6xO{BvVQ>? M3PuRXNCVkeHUh?=
HOP-92 M3PEWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjZWnRKSzVyPUK2MlQ5KG6P M120cHNCVkeHUh?=
HuO9 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml[2TWM2OD1{Nj63OkBvVQ>? MUXTRW5ITVJ?
SW962 NX[wXoZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfR[ZlKSzVyPUK2Mlc3KG6P M1HyU3NCVkeHUh?=
RS4-11 MofYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTJ4LkmxJI5O NIO5T5BUSU6JRWK=
NCI-H292 NUfXZ2pIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDVT5pOUUN3ME2yO{BvVQ>? NX;PN|FHW0GQR1XS
DB NWDNOHlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2flcGlEPTB;MkeuN|Yhdk1? MYDTRW5ITVJ?
SW1088 Mn36S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1fYOmlEPTB;MkiuNlkhdk1? NFzpOHRUSU6JRWK=
A204 M4TWdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml[4TWM2OD1{OD60O{BvVQ>? M1jadHNCVkeHUh?=
A3-KAW NY[1[nhDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlzrTWM2OD1{OD62OEBvVQ>? NXjl[IQ6W0GQR1XS
MV-4-11 NEC2bYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrLTWdkUUN3ME2yPE44KG6P NYSzWIxGW0GQR1XS
ES1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUnJR|UxRTJ6Lki0JI5O MXjTRW5ITVJ?
ONS-76 NH;3emZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPWdWdKSzVyPUK5MlA2KG6P NHT2dGhUSU6JRWK=
D-263MG M4L5[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{H6NWlEPTB;MkmuN|Uhdk1? M3\kXnNCVkeHUh?=
U-2-OS M1jIc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\EbINKSzVyPUK5MlUhdk1? MnrRV2FPT0WU
T98G MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojnTWM2OD1{OT64PEBvVQ>? MkPPV2FPT0WU
GI-ME-N NV3ocHpvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTJ7LkmxJI5O NVruVW1GW0GQR1XS
BHT-101 NVLtOYY{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{HwUGlEPTB;M{CuNFUhdk1? NYG2OoFYW0GQR1XS
NOS-1 M4rmZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTNyLkGyJI5O Ml3sV2FPT0WU
AsPC-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHTIcVFKSzVyPUOwMlIhdk1? MkHpV2FPT0WU
QIMR-WIL NU\uOpozT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fJcWlEPTB;M{CuOkBvVQ>? M1K3UnNCVkeHUh?=
JVM-3 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTNyLkizJI5O NYLtVI9zW0GQR1XS
KU-19-19 M{j0Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmLmTWM2OD1|MT6xN{BvVQ>? NEj4TYtUSU6JRWK=
OVCAR-8 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTNzLkK2JI5O NWD0b4NyW0GQR1XS
BEN MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTj[5FTUUN3ME2zNU43OyCwTR?= M4\6XHNCVkeHUh?=
BE-13 M4HqWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWj3VHpnUUN3ME2zNU45OiCwTR?= MX3TRW5ITVJ?
EW-18 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTNzLki2JI5O MorRV2FPT0WU
ECC10 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPOcVhCUUN3ME2zNU46PSCwTR?= NVvvUpNFW0GQR1XS
CTV-1 M3jCV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NULDVJVPUUN3ME2zNk45OiCwTR?= M4i3eXNCVkeHUh?=
COLO-800 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTN{LkmyJI5O MX3TRW5ITVJ?
A2058 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTN|LkK1JI5O Moj2V2FPT0WU
VM-CUB-1 Mn35S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LWSmlEPTB;M{OuOFMhdk1? NYPRRYFlW0GQR1XS
Ca9-22 NH;JdIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2eycWlEPTB;M{OuOVUhdk1? MkfEV2FPT0WU
COLO-684 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYfvPJVuUUN3ME2zN{42QCCwTR?= NHHE[IlUSU6JRWK=
RPMI-8226 NV\Oe5ppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXjEWYNLUUN3ME2zN{45OiCwTR?= MnTQV2FPT0WU
SK-NEP-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX21c3RXUUN3ME2zOE4yPSCwTR?= M{fxfXNCVkeHUh?=
Becker MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGX0c2lKSzVyPUO0MlIyKG6P NF;qXmFUSU6JRWK=
NCI-H28 NHnwXWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjjNWpKSzVyPUO0MlQ1KG6P NWnLWIRPW0GQR1XS
CAL-120 M2jPbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTN2LkeyJI5O MnS2V2FPT0WU
MDA-MB-157 M{P4XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWrJR|UxRTN3LkSxJI5O M4TnSHNCVkeHUh?=
OVCAR-5 NV\pXFl2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPxXWdKSzVyPUO1MlQ4KG6P NIj4dItUSU6JRWK=
LAMA-84 NHS1XXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3[5OGlEPTB;M{WuPFchdk1? NHP3UHZUSU6JRWK=
CAKI-1 Mn;PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE[ySFZKSzVyPUO2MlQ{KG6P NX\GN3gzW0GQR1XS
Daoy NFnDSmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXjyXFZsUUN3ME2zOk44KG6P Mk\5V2FPT0WU
CAL-62 NXjGfI1tT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\kTWM2OD1|Nj64OkBvVQ>? NE\Sd3BUSU6JRWK=
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LU-65 M1XmZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVnES5l6UUN3ME2xMlYzOjR7IN88US=> M2\uWHNCVkeHUh?=
NCI-H1304 NVnVflJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTFwNkW0PVgh|ryP NWPwb3BoW0GQR1XS
KARPAS-299 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\pTXhKSzVyPUGuO|k1PzlizszN MWHTRW5ITVJ?
NCI-H358 NWjyPY1jT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnXTWM2OD1zLkm1OVA{KM7:TR?= Ml74V2FPT0WU
OAW-28 NFLaV|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmD3TWM2OD1{LkC2PVE6KM7:TR?= NFX6RphUSU6JRWK=
C8166 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml31TWM2OD1{Lk[zN|kzKM7:TR?= NIPwOFBUSU6JRWK=
COLO-678 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1K4W2lEPTB;Mj64N|c3QCEQvF2= M164bnNCVkeHUh?=
SK-N-DZ M4XSTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfJTWM2OD1{Lki2N|gyKM7:TR?= NXHteVd{W0GQR1XS
NCI-H82 M33Cb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTJwOUCzOlkh|ryP NH3oNpVUSU6JRWK=
JVM-2 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGLBc2hKSzVyPUOuNFMyQDhizszN NU\qblh5W0GQR1XS
SW1116 M2izV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVXCU|U{UUN3ME2zMlA2PDFzIN88US=> MlnMV2FPT0WU
MDA-MB-453 NV[4U3p[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF[5cXFKSzVyPUOuNVA1OzlizszN NUDVXXJ7W0GQR1XS
Calu-6 NF7XSY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGP4OnVKSzVyPUOuNVk6PyEQvF2= MmLGV2FPT0WU
SHP-77 NXLnUIVjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTNwNUK4JO69VQ>? MUHTRW5ITVJ?
Capan-2 NHqzOYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLOXnhOUUN3ME20MlMzPThzIN88US=> M1nUOHNCVkeHUh?=
SW948 NXLEVWNOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPhWGNKSzVyPUSuO|Q4PzlizszN MYrTRW5ITVJ?
HDLM-2 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jwT2lEPTB;NT6wO|czPSEQvF2= MWjTRW5ITVJ?
LAN-6 NGjO[GJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3ZdJZKSzVyPU[uNlE1QTVizszN MUXTRW5ITVJ?
LU-135 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nyXWlEPTB;Nj60N|A4PyEQvF2= NILyfmxUSU6JRWK=
T84 NEfiU|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\oRWlEPTB;Nj65PFY1KM7:TR?= M{HDfXNCVkeHUh?=
CAPAN-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnjSTWM2OD15Lk[yNlM{KM7:TR?= NVm5SGV5W0GQR1XS
SW1417 NWC0dXg1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYPsUZByUUN3ME23MlkyPzNzIN88US=> MmfZV2FPT0WU
BALL-1 M3PTXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRThwNUC0NFkh|ryP MVHTRW5ITVJ?
HT-29 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWLJR|UxRTlwMEe1PVkh|ryP MV3TRW5ITVJ?
C3A NETVcWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mon3TWM2OD17Lki4N|k1KM7:TR?= MmDIV2FPT0WU
NCI-H1993 NXvqT5VnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;YRY0xUUN3ME2xNE42ODhzIN88US=> MVLTRW5ITVJ?
SK-MEL-1 MoX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWPJR|UxRTFzLk[yPFkh|ryP MVjTRW5ITVJ?
DU-145 NIDJUZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTF2LkWwOVIh|ryP NUDEVoVPW0GQR1XS
KP-N-YN NVTZeY5WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDLbpMzUUN3ME2xOE42OTB|IN88US=> MVLTRW5ITVJ?
CCRF-CEM MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmn0TWM2OD1zND63PFA6KM7:TR?= MUnTRW5ITVJ?
ZR-75-30 NY[1cFd5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHTU49KSzVyPUG2MlM{ODNizszN M3PLcXNCVkeHUh?=
A673 NHr2elRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTJyLkW1NFch|ryP MWfTRW5ITVJ?
K-562 Mke0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moe4TWM2OD1{OD60NVg{KM7:TR?= Mo[yV2FPT0WU

... Click to View More Cell Line Experimental Data

体内研究 BEZ235诱导肿瘤(69%)消退,而对体重增加没有统计学上显著的作用。总之,这些初步的体内功效研究结果表明,BEZ235单一口服给药时能够阻断疾病的发展,与其他抗癌药结合使用时能够增强疗效。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[2]

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体外蛋白激酶,PI3K,和mTOR实验:

PI3Kα, β, δ蛋白都由与p110全长蛋白相接的p85 N端的iSH2域组成,只是PI3Kα没有最后的20个氨基酸。PI3Kγ由p110全长蛋白去掉前144个氨基酸产生而来。所有PI3K蛋白在羧基末端加组氨酸标签便于纯化,然后克隆到pBlue-Bac4.5 (用于α, β,和δ亚型) 或者pVL1393 (用于γ 亚型) 质粒中。转染BaculoGold WT基因组DNA的不同的载体按说明书推荐的方法生产各自重组体杆状病毒及重组蛋白。使用激酶发光检测试剂盒测定BEZ235 (NVP-BEZ235)作用于PI3K的活力。在384孔板上进行激酶实验。在每个孔中加入50 nl的测试项目(溶在90%DMSO中)和5ul的反应buffer,反应buffer包含10 μg/ml PI基质 (l-α-磷脂酰肌醇; 由Avanti Polar Lipids提供;预备在3%辛基葡萄糖苷中),然后加入PI3K 蛋白(p110α, p110β, p110δ,和p110γ分别为10, 25, 10,和150 nM)。加入预备在反应buffer中的5 ul 1 µM 的ATP反应开始,反应进行60分钟 (测p110α, p110β, p110δ)或者120分钟(测p110γ),随后加入10ul的荧光激酶buffer终止反应。数据用Synergy 2 阅读器阅读用于荧光测试。
细胞实验:

[1]

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  • Cell lines: HCT116, DLD-1, SW480
  • Concentrations: 0-1 μM
  • Incubation Time: 48小时
  • Method:

    HCT116 (PIK3CA突变型; 激酶域在H1047R), DLD-1 (PIK3CA突变型;螺旋域在E545K), SW480 (PIK3CA 野生型)人类CRC细胞系,同基因型的DLD-1 PIK3CA突变和野生型细胞培养在含10%FBS和1×青霉素/链霉素的培养基中。细胞按不同的初始密度加入(HCT116: 3000个细胞/每孔, DLD-1: 5500个细胞/每孔, SW480: 4500个细胞/每孔, DLD-1 PIK3CA突变型: 7000个细胞/每孔, DLD-1 PIK3CA野生型: 9000个细胞/每孔),用来计算不同的生长动力学。16个小时后,细胞加入浓度越来越高的BEZ235中进行温育,含有药物的培养基24小时更换一次。根据产品说明书,加入细胞16小时和药物处理48小时,使用单溶液细胞增殖检测试剂盒以比色法检测细胞活力。与没有用药物处理正在生长的细胞相比,药物处理的细胞的活力也逐渐趋于正常化。使用GraphPad Prism 5软件用4个参数的回归曲线计算IC50值。用于western blot 分析,细胞用0 nM 或者最高抑制剂量(500 nM) BEZ235处理 2, 6, 24, 或者48 小时。


    (Only for Reference)
动物实验:

[2]

+ 展开
  • Animal Models: 雌性Harlan无胸腺裸鼠
  • Formulation: NMP/聚乙二醇300(10/90,v/v)
  • Dosages: 45 mg/kg
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMF 18 mg/mL warmed (38.33 mM)
DMSO 0.01 mg/mL (0.02 mM)
Water Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用:
NMP+polyethylene glycol 300 (10+90, v+v)
30 mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 469.55
化学式

C30H23N5O

CAS号 915019-65-7
稳定性 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00620594 Completed Breast Cancer|Advanced Solid Tumors|Cowden Syndrome Novartis Pharmaceuticals|Novartis December 21, 2006 Phase 1
NCT01856101 Terminated Carcinoma Transitional Cell Cliniques universitaires Saint-Luc- Université Catholique de Louvain|Novartis February 2013 Phase 2
NCT01717898 Terminated Castrate-resistant Prostate Cancer Patients. Charles Ryan|Novartis Pharmaceuticals|University of California, San Francisco January 2013 Phase 1|Phase 2
NCT01658436 Completed Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis November 2012 Phase 2
NCT01628913 Terminated Pancreatic Neuroendocrine Tumors (pNET) Novartis Pharmaceuticals|Novartis October 2012 Phase 2
NCT01690871 Withdrawn Malignant PEComa (Perivascular Epithelioid Cell Tumors) Novartis Pharmaceuticals|Novartis September 2012 Phase 2

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    With difficulties in dissolving BEZ235, How can I improve its solubility?

  • 回答:

    For in vivo study, we suggest the vehicle solution NMP/polyethylene glycol 300 (10/90, v/v). Please dissolve BEZ235 in NMP as more as possible. You can sonicate and warm it in water bath for a while. Then dilute with PEG 300.

PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

相关PI3K产品

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID